The adherence of cells to each other and to the extracellular matrix, as well as the cellular signals transduced as a consequence of such binding, are of fundamental importance to the development and maintenance of body form and function. A number of molecules mediating cell adhesion have been identified and characterized at the molecular level both in vertebrates and in invertebrates. Many cell surface cell adhesion molecules (CAMs) are of three major types: 1) members of the immunoglobulin supergene family, which mediate calcium independent adhesion, 2) cadherins, which mediate calcium-dependent adhesion and are important structural components of adherence junctions, and 3) integrins, a family of heterodimeric proteins which can facilitate adhesion of cells both to each other and to the extracellular matrix.
CAMs may have multiple ligands. They can mediate adhesion by the interaction of a CAM on one cell with the identical CAM on another cell (homophilic binding), or they can mediate adhesion by interacting with different CAMs or extracellular matrix molecules (heterophilic binding). For example, contactin, a member of the immunoglobulin gene superfamily, can undergo homophilic binding or can bind heterophilically to other cell surface molecules such as the L1 antigen or to extracellular matrix molecules of the tenascin family. One extracellular matrix ligand for contactin is janusin, which is a member of the tenascin-R family. Janusin is closely related to tenascin in its patterns of epidermal growth factor, fibronectin type III and fibrinogen-like domains. In rodents, it is synthesized by oligodendrocytes and subpopulations of neurons at late developmental stages in the central nervous system. It can promote cell adhesion or anti-adhesion, depending on the neural cell type with which it interacts, promoting neurite outgrowth of some neural cell types and inhibiting neurite outgrowth from other neuronal populations. The repulsive response of neurons to janusin may be mediated by contactin. Janusin has been identified in rodents (A. Faissner, et al. 1990. Neurochem. 54:1004-1015) and the rat gene has been cloned (B. Fuss, et al. 1991. J. Neurosci. Res. 29:299-307) and sequenced (B. Fuss, et al. 1993. J. Cell Biol. 120:1237-1249). The chicken homolog of janusin, referred to as restrictin, has also been identified and characterized (U. Norenberg, et al. 1992. Neuron 8:849-863).